GABA(A) RECEPTOR SUBUNIT EXPRESSION CHANGES IN THE RAT CEREBELLUM ANDCEREBRAL-CORTEX DURING AGING

Significant aging-related decreased expression of various GABA(A)R sub unit mRNAs (alpha(1),gamma(2),beta(2),beta(3), and delta) was found in both cerebellum and cerebral cortex using quantitative dot blot and i n situ hybridization techniques. Contrary to the other subunits, the c u, mRNA expression was significantly increased in the aged cerebellum. Parallel age-related changes in protein expression for gamma(2) and b eta(2/3) (decrease) and alpha(6) (increase) were revealed in cerebellu m by quantitative immunocytochemistry. However, no significant changes in Lu, protein expression nor in the number or affinity of [H-3]zolpi dem binding sites were detected in cerebellum even though cr, mRNA exp ression was significantly decreased in the aged rat. Age-related incre ased expression of Lu, mRNA and protein in the cerebellum was accompan ied by no significant changes in the number of diazepam-insensitive [H -3]Ro15-4513 binding sites. In the cerebral cortex, no changes in the protein expression of the main GABA(A) receptor subunits (alpha(1),gam ma(2),beta(2/3)) were observed which contrasted with the age-related d ecreased expression of the corresponding mRNAs. No significant changes in the number or affinity of [SH]zolpidem binding sites were observed in the cerebral cortex. Thus, age-related changes in the mRNA express ion of a particular subunit does not necessarily lead to similar chang es in protein or assembly into mature GABA, receptors. The results rev eal the existence of complex regulatory mechanisms of GABA, receptor e xpression, at the transcriptional, translational and post-translationa l and/or assembly levels, which vary with the subunit and brain area.